Antagonism by fenamates and like-acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea-pig.
1. Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive.2. The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>glafenine>ibufenac.3. Of eight other drugs tested, chlorpromazine, phenoxybenzamine and four others were inactive, whereas phenelzine and mebanazine possessed activity.4. In tests at two dose-levels of meclofenamate, the dose-ratio of bradykinin increased proportionately with the dose of meclofenamate.5. The anti-bradykinin effect of meclofenamate was still observed after destruction of the brain and spinal cord, after bilateral adrenalectomy or after blockade of beta-receptors for adrenaline.6. Meclofenamate did not release catecholamines from the adrenal medulla or prevent such a release by bradykinin given intra-arterially.7. The fenamates and like-acting drugs reduced the intensity of anaphylactic bronchoconstriction in guinea-pigs treated with mepyramine or propranolol. The descending order of potency was meclofenamate>flufenamate>mefenamate.8. Dose / response curves for the antagonism of anaphylactic bronchoconstriction by the fenamates, in the presence of propranolol, turned downwards at high doses.9. These findings suggest that the fenamates may find a useful place in the treatment of bronchial asthma or other conditions involving allergic ventilatory impairment.
D000313:Adrenal Medulla / Q000378:metabolism; D000315:Adrenalectomy; D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000941:Antigens; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D001921:Brain; D001980:Bronchi / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D003250:Constriction / Q000187:drug effects; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D010624:Phenelzine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011955:Receptors, Drug; D013116:Spinal Cord
D000893:Anti-Inflammatory Agents; D000941:Antigens; D002395:Catecholamines; D010648:Phenylacetates; D011955:Receptors, Drug; D010643:Phenoxybenzamine; D011433:Propranolol; D010624:Phenelzine; D001920:Bradykinin; D002746:Chlorpromazine; D007213:Indomethacin